BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) represents the largest group of pediatric malignancies with long-term survival rates of more than 80% achieved in developed countries. Epidemiological data and survival rates of childhood ALL in Lithuania were lacking. Therefore, the aim of this study was to analyze the population-based long-term treatment results of childhood ALL in Lithuania during 1992-2012. MATERIALS AND METHODS: Data of all 459 children with T-lineage and B-cell precursor ALL treated in Lithuania from 1992 to 2012 were collected and analyzed. Results were compared among four time-periods: 1992-1996 (N=132), 1997-2002 (N=136), 2003-2008 (N=109) and 2009-2012 (N=82). RESULTS: The incidence of childhood ALL in Lithuania was 3.2-3.6 cases per 100000 children per year during the study period. Five-year probability of event-free survival increased from 50%± 4% in 1992-1996 to 71%± 4% in 2003-2008 (P<0.001). Five-year cumulative incidence of relapses reduced from 27%± 4.5% in 1992-1996 to 14%± 3.6% in 2003-2008 (P=0.042). After introduction of high-dose methotrexate of 5 g/m(2), cumulative incidence of CNS-involving relapses reduced from 17%± 3.9% in 1992-1996 to 1%± 1.0% in 2003-2008 (P<0.001). Trend for further improvement in survival was seen in 2009-2012 when Lithuania joined international the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL-2008 treatment protocol. CONCLUSIONS: Cure rates of childhood ALL in Lithuania are improving steadily and are now approaching those reported by the largest international study groups. The reasons for such a positive effect are both better financial support for treatment of children with cancer in Lithuania and international collaboration with joining international treatment protocol for childhood ALL.